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CASE REPORTTetramine poisoningWe report on two patients who presented with status epilepticus dueto ingestion of rat poison containing tetramine. Both had eaten thesame meal, subsequently presumed to be the source of the poison.Physical examination and investigation were unremarkable and diag-nosis was based on patient history. Seizures were ultimately control-led with ketamine, after unsuccessful attempt of benzodiazepine andsodium thiopentone. One week after poisoning, both patientsunderwent one session of high-volume haemofiltration followed bycharcoal haemoperfusion to eliminate the toxin from the body. Plasmatetramine levels then decreased from 0.95 µg/mL to 0.35 µg/mL andfrom 0.53 µg/mL to 0.40 µg/mL, respectively.Case reportsKey words:Case 1
A 38-year-old construction worker was admitted with status epilepticus
in January 2003. He had a history of epilepsy but had defaulted from
follow-up and taken no anticonvulsant drugs for 3 months. While in the
Accident and Emergency Department, he had a generalised tonic-clonic
convulsion that lasted 30 minutes. His temperature was 37ΟC andGlasgow Coma Scale (GCS) score was 3/15. There was no neck rigidity
and both pupils were dilated and reactive. There were no localising signs
and no external evidence of head injury. Cardiovascular examination was
unremarkable: pulse, 110 beats per minute regular; blood pressure,
180/100 mm Hg; electrocardiogram (ECG), normal. His chest was clear
to auscultation and pulse oximeter read 95% on room air. The seizure
remained uncontrolled following administration of lorazepam 8 mg,diazepam 10 mg, and phenytoin 750 mg. He was intubated and plain
computed tomography of the brain revealed mild cerebral oedema.Intensive Care Unit, North District
Results of laboratory investigations were shown in the Table. Osmolar
Hospital, Sheung Shui, Hong Kong
gap, calcium, glucose, ammonia, and liver function tests were normal.
CM Chau, MB, BS, FHKCAIntensive Care Unit, Pamela YoudeNethersole Eastern Hospital, Chai Wan,
A further seizure occurred despite rapid escalation of anticonvulsant
Hong Kong
therapy (midazolam 14 mg immediately followed by 10 mg/h, phenytoin
2 g, thiopentone 2 g loading followed by 375 mg/h). A ketamine infusion
Department of Intensive Care Medicine,Singapore General Hospital, Singapore
at a dose of 120 mg/h eventually brought the seizure under control.
Sodium thiopentone, midazolam, and ketamine infusion were graduallystopped after 16 hours of seizure-free activity on electroencephalography
Correspondence to: Dr CM Chau(e-mail: [email protected])
Hong Kong Med J Vol 11 No 6 December 2005 511
Table. Laboratory findings
prescribed blood flow rate of 200 mL/min. Tinzaparin
was again used as anticoagulant. This time, plasma te-
tramine level decreased from 0.53 µg/mL to 0.40 µg/mL,
a reduction of 25%. Blood was taken 5 minutes after
cessation of blood flow during both HVHF and HP.
The patient remained in the intensive care unit
(ICU) for 16 days and was then discharged. He had
normal mental function at 1-month follow-up.Case 2
A 33-year-old woman, who shared the same meal with
the patient in case 1, presented with vomiting that
was successfully controlled with prochlorperazine. She
refused admission but presented again the followingday with confusion and a generalised tonic-clonicconvulsion. Examination revealed a GCS score of15/15 but no focal signs. She was afebrile and
Questioning of the patient’s wife revealed that
cardiovascular and laboratory examinations were
her husband’s colleague (patient in case 2), who
unremarkable: blood pressure, 117/75 mm Hg; pulse,
shared the same meal, had also had a convulsion.
85 beats per minute; pulse oximeter 95% on room air;
A dog that ate the remains of the meal had convul-
and ECG normal. Her GCS score decreased to 9/15
sions and was found dead the following day. Probable
after a further seizure and she was intubated and given
food or drug poisoning was suspected. Activated
charcoal 50 g every 6 hours was commenced onadmission and continued for 2 days. Plasma cholineste-
She was extubated 5 hours later. Tetramine was
rase level was 6606 IU/L. Methaemoglobin level was
detected in vomitus and blood (0.54 µg/mL) on day 7.
0.3%. Serum lead was normal (0.3 µmol/L) and the
She was confused but experienced no further seizures.
arsenate level was negative. Blood and urine were
She was discharged on day 10 having made a full
negative for salicylate, paracetamol, and cannabinoids.
The patient was extubated on day 7. He remained
Discussion
confused and exhibited frequent facial twitching.Tetramine, the active component of a rat poison
Tetramethylene disulphotetramine (TETS), commonly
‘dushuqiang’, was identified in vomitus 1 week after
called tetramine, is an odourless and tasteless small
admission. Intravenous pyridoxine 50 mg daily was
molecule with MV 248. It binds to the gamma-
prescribed for 5 days from day 7 onward. One session
aminobutyric acid (GABA) receptor on the neuronal
of high-volume haemofiltration (HVHF) followed
cell membrane and blocks the chloride channels.1,2
by a session of charcoal haemoperfusion (HP) were
Available pharmacokinetic data are incomplete
and sometimes contradictory. Both reversible2 andirreversible binding3 to the GABA receptors have
been described. The TETS can be absorbed through
on-line haemofiltration system and a high-flux
the gastro-intestinal tract and respiratory system.
polysulphone diafilter (APS900, Asahi dialyzer, Japan;
Thereafter, it is rapidly distributed to various body
1.8 m2, removes molecules of up to 66 000 dalton).
tissues and organs. It has a high volume of distribution,
Blood flow was set at 200 mL/min and ultrafiltration
a slow metabolism, and is excreted unchanged in the
flow at 200 mL/min. Predilution replacement fluid was
urine and stool. It can remain in the body for up to 6
given at 200 mL/min for 10 hours. Tinzaparin was used
months. The lethal dose 50% for humans is 0.1 mg/kg
as anticoagulant. The plasma tetramine level decreased
and there is no specific and effective antidote reported
by 63% from 0.95 µg/mL to 0.35 µg/mL. The follow-
in the literature at the time of writing.2,3
ing day the tetramine level increased to 0.53 µg/mL: a6-hour HP was performed with a cartridge containing
The quoted toxic and lethal ranges for tetramine
300 g of activated charcoal (Adsorba 300C; Gambro
are 0.002 to 0.369 µg/mL and 0.64 to 5.49 µg/mL,
Lundia AB, Sweden) coated with cellulose and at a
respectively.4 In mild-to-moderate poisoning, symp-
512 Hong Kong Med J Vol 11 No 6 December 2005
toms include headache, dizziness, nausea, vomiting,
High-volume haemofiltration may be an alterna-
abdominal pain, bradycardia, tachycardia, twitching,
tive to HP since the charcoal cartridge for the latter is
agitation, and visual and auditory hallucinations. In
not readily available in most ICUs and its shell-life is
severe cases, status epilepticus, coma, and multi-
limited. Although the success of haemofiltration
organ failure can occur. Electroencephalography
has not been extensively evaluated, the number of suc-
demonstrates generalised slow waves and spikes.
cessful case reports is increasing. Its use in tetramine
Onset time is rapid and occurs within 30 minutes of
exposure and may last up to 13 hours. A fatality rateas high as 3.67% has been reported.5 Diagnosis de-
In the first patient reported here, the plasma
pends principally on history and clinical presentation.
tetramine level was decreased by both HVHF and HP.
Detection of tetramine in blood or the excreta by gas
The drop in plasma tetramine level was greater
chromatography/mass spectroscopy is confirmatory.
following HVHF (63%) than charcoal HP (25%).The increase in tetramine level from 0.35 µg/mL to
0.53 µg/mL 12 hours after HVHF was compatible with
antidotal effect. Animal and human studies reveal
the rebound phenomenon and redistribution of the toxin
that it prolongs the latent period of convulsions and
from tissue stores to plasma. The difference in plasma
reduces convulsive time and mortality.6,7 Binding of
level reduction following HVHF and HP may have
GABA in the brain is also enhanced. The anticonvul-
been due to different treatment durations and the
sant effect is increased by high-dose vitamin B6
mechanisms involved. It is difficult to compare the
and diazepam.7-9 Dimercaptopropanesulphonate is
efficacy of toxin removal by HVHF and HP if the
available in some major hospitals in Hong Kong.
amount of tetramine removed cannot be quantified.
Extracorporeal toxin removal has been frequently
As there is limited immediate access to charcoal
performed in China by plasma exchange, HP, and
HP in most ICUs, HVHF can be considered an
haemodialysis with variable results.2,4,10,11 Plasma
alternative treatment for tetramine poisoning.
exchange is reported to be more successful in cases ofsevere intoxication. Haemoperfusion is nonetheless
Conclusion
more common and is associated with less reboundphenomena and stable haemodynamics. Haemodialy-
Early and adequate resuscitation combined with
sis is least useful unless the patient is in renal failure.
seizure control are crucial to the management of acutetetramine poisoning. Ketamine and conventional
The efficacy of ketamine in prolonged status
anticonvulsant drugs may have synergistic and
epilepticus has been demonstrated in both animal
additive effects in the management of refractory
models and humans.12,13 It decreases the excitatory
status epilepticus. High-volume haemofiltration may
effects of glutamate and other excitatory neurotrans-
be an alternative to charcoal HP in tetramine poisoning.
mitters through blockade of the N-methyl-D-aspartate–gated calcium channel. Ketamine and conventional
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